<b>Nestin and WT-1: Potential Interplay in Astrocytoma Tumor Biology</b>

Background: Glial cells are the origin of gliomas, a diverse group of brain tumors including Astrocytoma, Oligodendrogliomas and Ependymoma, classified based on their cellular origin. The St. Anne/Mayo grading system evaluates key histological features such as necrosis, endothelial proliferation, mitotic activity and cellular atypia to determine tumor grade and guide treatment. Although less common than other cancers, CNS malignancies cause significant morbidity and mortality, with thousands of new cases and deaths reported annually worldwide. Objective: The purpose of the current study was to examine the relationship between immunoexpression of the Nestin protein and WT-1 gene and various grades of Astrocytoma. Methods: A cross-sectional study was carried out at the Pathology Department of Basic Medical Science Institutes, Jinnah Postgraduate Medical College in Karachi, Sindh, Pakistan, from January 2019 to December 2022. There were 60 Astrocytoma cases in this investigation. All the cases of various grades of Astrocytoma were received in the department of Pathology, Basic Medical Sciences Institute, Jinnah Post Graduate Medical Center, Karachi were deeply reviewed and were included in this study. Results: Sixty examples of Astrocytoma were immunostained with WT-1 and Nestin. 86.7% of Astrocytoma cases had Nestin positivity, while 93.3% had positive WT-1 immunostaining. It was shown that there was a significant association (p<0.001) between the score of the both immunomarker Nestin and WT-1 and the grade of the tumor, with a higher score for high-grade (grade III and grade IV) and a lower score for low-grade (grade I and grade II) Astrocytoma. Conclusion: Nestin and WT1 immunoexpression is positively correlated with higher tumor grade and enhanced mitotic activity, suggesting that they may be useful prognostic indicators in Astrocytoma. Additionally, their strong association with tumor aggressiveness highlights Nestin and WT1's potential as therapeutic targets as well as prognostic factors, opening the door to more individualize and efficient Astrocytoma management treatment plans.